Allopregnanolone, the Neuromodulator Turned Therapeutic Agent: Thank You, Next?

Pharmacological treatments, including finasteride and oral contraceptives, that inhibit 5α-RI, which results in a blood and brain allopregnanolone decrease also affect subunit expression of GABAA receptor and are associated with mood symptoms and suicide and are part of post-finasteride syndrome. Post-finasteride syndrome, in addition to depression, anxiety and cognitive deficits also induces sexually-related side effects, such as loss of libido, erectile dysfunction, decreased arousal and difficulty in achieving an orgasm that persist despite drug withdrawal. Evidence suggests during pregnancy and across the estrous cycle a switch of extrasynaptic δ with synaptic γ2 subunits may be operative. Rapid and dynamic changes among synaptic and extrasynaptic GABAA receptor conformation in areas that regulate cognitive functions and emotions, including the hippocampus have been reported.

Pinna G (2020) Allopregnanolone, the Neuromodulator Turned Therapeutic Agent: Thank You, Next? Front. Endocrinol. 11:236. doi: 10.3389/fendo.2020.00236 [Frontiers in Endocrinology]